title: Coronary microvascular dysfunction is an early feature of cardiac involvement in patients with Anderson-Fabry disease.
abstract: OBJECTIVE
  Male patients with Anderson-Fabry disease (AFD) often exhibit cardiac involvement, characterized by LV hypertrophy (LVH), associated with severe coronary microvascular dysfunction (CMD). Whether CMD is present in patients without LVH, particularly when female, remains unresolved. The aim of the study was to investigate the presence of CMD by positron emission tomography (PET) in AFD patients of both genders, with and without evidence of LVH.
  
  
  RESULTS
  We assessed myocardial blood flow following dipyridamole infusion (Dip-MBF) with 13N-labelled ammonia by PET in 30 AFD patients (age 51 ± 13 years; 18 females) and in 24 healthy controls. LVH was defined as echocardiographic maximal LV wall thickness ≥13 mm. LVH was present in 67% of patients (n = 20; 10 males and 10 females). Dip-MBF was reduced in all patients compared with controls (1.8 ± 0.5 and 3.2 ± 0.5 mL/min/g, respectively, P < 0.001). For both genders, flow impairment was most severe in patients with LVH (1.4 ± 0.5 mL/min/g in males and 1.9 ± 0.5 mL/min/g in females), but was also evident in those without LVH (1.8 ± 0.3 mL/min/g in males and 2.1 ± 0.4 mL/min/g in females; overall P = 0.064 vs. patients with LVH). Analysis of variance (ANOVA) for the 17 LV segments showed marked regional heterogeneity of MBF in AFD (F = 4.46, P < 0.01), with prevalent hypoperfusion of the apical region. Conversely, controls showed homogeneous LV perfusion (F = 1.25, P = 0.23).
  
  
  CONCLUSIONS
  Coronary microvascular function is markedly impaired in AFD patients irrespective of LVH and gender. CMD may represent the only sign of cardiac involvement in AFD patients, with potentially important implications for clinical management.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Tomberli
authors.forename: Franco
authors.initials: F
authors.lastname: Cecchi
authors.forename: Roberto
authors.initials: R
authors.lastname: Sciagrà
authors.forename: Valentina
authors.initials: V
authors.lastname: Berti
authors.forename: Francesca
authors.initials: F
authors.lastname: Lisi
authors.forename: Francesca
authors.initials: F
authors.lastname: Torricelli
authors.forename: Amelia
authors.initials: A
authors.lastname: Morrone
authors.forename: Gabriele
authors.initials: G
authors.lastname: Castelli
authors.forename: Magdi H
authors.initials: MH
authors.lastname: Yacoub
authors.forename: Iacopo
authors.initials: I
authors.lastname: Olivotto
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D003326:Coronary Circulation; D003430:Cross-Sectional Studies; D004452:Echocardiography / Q000379:methods; D000795:Fabry Disease / Q000150:complications*; D005260:Female; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D007558:Italy; D008297:Male; D055806:Microvessels / Q000503:physiopathology*; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D012737:Sex Factors
keywords: Coronary microvascular dysfunction; Early phenotype; Fabry disease; PET